scholarly journals Correlation of Cytomegalovirus (CMV) Disease Severity and Mortality With CMV Viral Burden in CMV-Seropositive Donor and CMV-Seronegative Solid Organ Transplant Recipients

2019 ◽  
Vol 6 (2) ◽  
Author(s):  
Jacqueline M McBride ◽  
Daniel Sheinson ◽  
Jenny Jiang ◽  
Nicholas Lewin-Koh ◽  
Barbara G Werner ◽  
...  
Keyword(s):  
Viral Load ◽  
Disease Severity ◽  
Quantitative Polymerase Chain Reaction ◽  
Solid Organ Transplantation ◽  
Area Under The Curve ◽  
World Health ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Viral Burden ◽  
Cmv Disease

Abstract Background The rate of cytomegalovirus (CMV) viral load increase and peak viral loads are associated with CMV disease in kidney and liver transplant recipients, but relationships to disease severity or mortality have not been shown. Methods Using stored serial serum specimens from renal (n = 59) and liver (n = 35) transplant recipients (D+R-; CMV-seropositive donors, CMV-seronegative recipients) from 2 prospective, randomized, controlled, interventional prophylaxis trials of CMV immune globulin (CMVIG), CMV viral load was measured using the COBAS quantitative polymerase chain reaction assay and the World Health Organization CMV standard. Patients with severe CMV-associated disease were classified according to trial definitions. Pairwise comparisons of mean viral load among deceased, surviving diseased, and nondiseased patients were analyzed by 2-way analysis of variance. To determine if viral load could predict mortality, receiver operating characteristic (ROC) curves were constructed using area under the curve (AUC) of the viral load and peak viral concentration (Vmax). Results Viral load (mean log10 [AUC], peak viral load [Vmax]) for patients with severe CMV disease was significantly higher compared with nondiseased patients (P < .001). Similarly, higher viral burden was significantly associated with mortality (P < .001). Viral load AUC and Vmax AUROCs for predicting mortality were 0.796 and 0.824, respectively, for renal patients, and 0.769 and 0.807, respectively, for liver patients. Conclusions Using specimens from studies preceding the antiviral prophylaxis era, CMV viral load was associated with severe CMV disease and death, supporting CMV viral load quantification as a proxy for CMV disease severity and disease-associated mortality end points in solid organ transplantation.

scholarly journals Molecular Detection and Glycoprotein B (UL55) Genotyping of Cytomegalovirus among Sudanese Renal Transplant Recipients

2019 ◽  
Author(s):  
Hind Haidar Ahmed ◽  
Alfadil Elobeid Omer ◽  
Hisham N. Altyab
Keyword(s):  
Viral Load ◽  
Renal Transplant ◽  
Glycoprotein B ◽  
P Value ◽  
Solid Organ ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Viral Loads ◽  
Significant Difference ◽  
Cmv Disease

Abstract Background Cytomegalovirus (CMV) is the most common opportunistic pathogen among solid organ transplant recipients’ especially renal transplants with significant morbidity and mortality. This study was designed to detect CMV DNA and to determine the frequency of different glycoprotein B (UL55) genotypes among Sudanese renal transplant recipients. Methods One hundred and four renal transplant recipients were included in this study. A blood specimen was collected from each recipient. DNA was extracted from plasma using QIAamp DNA mini kit. CMV amplification and quantification (estimation of viral load) was performed using CMV Real – RT Quant kits. Genotyping of Human CMV gB was carried out by nested PCR and sequencing of the highly diverse region of glycoprotein B. Results Cytomegalovirus (CMV) DNA (viremia) was detected in 40/104 (38.5%) of renal transplant recipients. The average of CMV DNA viral load was 358 x104 copies/ml (6.5 log10) ranged from 62 copies/ml (1.8 log 10) to 1.43x108 copies/ml (9 log10). CMV viremia was detected in (60%) of recipients of less than 1-12 months, (17%) of 13-24, (10%) of 25-36, (5%) of 37- 48 and (8%) in more than 48 months post-transplantation with no significant association (P. value = 0.296) between CMV viremia and post renal transplantation time. The association between the type of immunosuppressive drugs and high viral loads (more than 1000 copies /ml) showed a significant difference (P. value =0.05). The correlation between CMV loads of more than 1000 copies/ml and the presence of symptoms of CMV disease were highly significant (P.value =0.00). Fever 7(41%), fever and leucopenia 6(35%) and gastrointestinal disease 4(24%) were the most common presenting symptoms of CMV disease. CMV-genotyping revealed 8 cases (80%) for gB3, and 2 cases (20%) for gB4 genotypes. The most frequent genotype among Sudanese renal transplant recipients was gB3 and no mixed genotypes were observed. Conclusions The frequency of CMV DNA is high among Sudanese renal transplant recipients. CMV viremia viral loads were slightly lower in asymptomatic patients. CMV gB3 is the most predominant glycoprotein B genotype in Sudanese renal transplant recipients.

scholarly journals Quantitation of Cytomegalovirus: Methodologic Aspects and Clinical Applications

1998 ◽  
Vol 11 (3) ◽  
pp. 533-554 ◽  
Author(s):  
Michael Boeckh ◽  
Guy Boivin
Keyword(s):  
Viral Load ◽  
Disease Activity ◽  
Antiviral Treatment ◽  
Antigen Detection ◽  
Molecular Techniques ◽  
Quantitative Detection ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Detection Techniques ◽  
Cmv Disease

SUMMARY Cytomegalovirus (CMV) is an important pathogen in transplant recipients and human immunodeficiency virus (HIV)-infected individuals. Major progress has been made in developing quantitative detection methods for CMV in recent years. Due to their high sensitivity, these assays can detect CMV early, and quantitation may be useful in predicting the patient’s risk for disease and in monitoring the effect of antiviral therapy. This review discusses methodological aspects of currently used quantitative assays for CMV (i.e., viral culture techniques, antigen detection assays, DNA detection assays including PCR, branched-DNA assay, and the DNA hybrid capture assay) and addresses the correlation of systemic and site-specific CMV load and CMV disease in different populations of immunosuppressed patients as well as the response to antiviral treatment. To date, direct antigen detection and molecular techniques have largely replaced traditional culture-based techniques for CMV quantitation. In general, a high systemic CMV load is correlated with CMV disease. This correlation is strong in the HIV-infected population and in solid-organ transplant recipients but less clear in allogeneic marrow transplant recipients. Measuring the viral load at specific anatomic sites may be an alternative way to assess disease activity in situations where the systemic viral load correlates poorly with disease activity. A reduction of the systemic CMV load also correlates with a response to antiviral treatment, but more research is needed to evaluate the role of viral load as a surrogate marker for drug resistance. Due to the widespread use of quantitative CMV detection techniques to direct and monitor antiviral treatment, there is a great need for an assessment of the reproducibility of test results and better standardization of the assays.

scholarly journals Comparison of Standardized Cytomegalovirus (CMV) Viral Load Thresholds in Whole Blood and Plasma of Solid Organ and Hematopoietic Stem Cell Transplant Recipients with CMV Infection and Disease

2017 ◽  
Vol 4 (3) ◽  
Author(s):  
M Veronica Dioverti ◽  
Brian D Lahr ◽  
Jeffrey J Germer ◽  
Joseph D Yao ◽  
Michelle L Gartner ◽  
...  
Keyword(s):  
Stem Cell ◽  
Viral Load ◽  
Hematopoietic Stem Cell ◽  
Whole Blood ◽  
Asymptomatic Infection ◽  
Solid Organ ◽  
Cell Transplant ◽  
Transplant Recipients ◽  
Hematopoietic Stem ◽  
Cmv Disease

Abstract Background Quantification of cytomegalovirus (CMV) deoxyribonucleic acid (DNA) has important diagnostic, prognostic, and therapeutic implications in the management of transplant recipients. We aimed to assess a viral load in plasma and whole blood that distinguishes CMV disease from asymptomatic infection in a cohort of solid organ and hematopoietic stem cell transplantation. Methods We prospectively measured and compared CMV viral load in paired plasma and whole blood samples collected from transplant recipients with CMV infection and disease. Cytomegalovirus viral loads were determined by a commercially available US Food and Drug Administration-approved quantitative assay (COBAS AmpliPrep/COBAS TaqMan CMV Test [CAP/CTM CMV]) calibrated to the first World Health Organization International Standard for CMV DNA quantification. Results Moderate agreement of CMV viral load was observed between plasma and whole blood, with 31% of samples having discordant findings, particularly among samples with low DNA levels. Among the subset of samples where both paired samples had quantifiable levels, we observed a systematic bias that reflected higher viral load in whole blood compared with plasma. Based on receiver operating curve analysis, an initial plasma CMV viral load threshold of 1700 IU/mL in solid organ transplant recipients (sensitivity 80%, specificity 74%) and 1350 IU/mL in allogeneic hematopoietic stem cell transplant recipients (sensitivity 87%, specificity 87%) distinguished CMV disease and asymptomatic infection. Conclusions This study identifies standardized viral load thresholds that distinguish CMV disease from asymptomatic infection using CAP/CTM CMV assay. We propose these thresholds as potential triggers to be evaluated in prospective studies of preemptive therapy. Plasma was better than whole blood for measuring viral load using the CAP/CTM CMV assay.

Cytomegalovirus in Solid Organ Transplant Recipients: Clinical Updates, Challenges and Future Directions

2020 ◽  
Vol 26 (28) ◽  
pp. 3497-3506
Author(s):  
Raymund R. Razonable
Keyword(s):  
Organ Transplantation ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Cmv Infection ◽  
Future Directions ◽  
Prevention And Treatment ◽  
Solid Organ Transplant Recipients

Cytomegalovirus is the classic opportunistic infection after solid organ transplantation. This review will discuss updates and future directions in the diagnosis, prevention and treatment of CMV infection in solid organ transplant recipients. Antiviral prophylaxis and pre-emptive therapy are the mainstays of CMV prevention, but they should not be mutually exclusive and each strategy should be considered depending on a specific situation. The lack of a widely applicable viral load threshold for diagnosis and preemptive therapy is emphasized as a major factor that should pave the way for an individualized approach to prevention. Valganciclovir and intravenous ganciclovir remain as drugs of choice for CMV management, and strategies for managing drug-resistant CMV infection are enumerated. There is increasing use of CMV-specific cell-mediated immune assays to stratify the risk of CMV infection after solid organ transplantation, and their potential role in optimizing CMV prevention and treatment efforts is discussed.

scholarly journals Adenovirus viremia may predict adenovirus pneumonia severity in immunocompetent children

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ruimu Zhang ◽  
Hongmei Wang ◽  
Shufeng Tian ◽  
Jikui Deng
Keyword(s):  
Risk Factors ◽  
Viral Load ◽  
Disease Severity ◽  
Mycoplasma Pneumoniae ◽  
Quantitative Polymerase Chain Reaction ◽  
Univariate Analysis ◽  
Clinical Manifestations ◽  
Pneumonia Severity ◽  
Adenovirus Pneumonia ◽  
Blood Viral Load

Abstract Background Previous studies have demonstrated an association between adenovirus viremia and disease severity in immunocompromised children. However, few studies have focused on this association in immunocompetent children. This study explored the association between adenovirus viremia and adenovirus pneumonia severity in immunocompetent children. Methods We performed a retrospective, observational study of immunocompetent children with adenovirus pneumonia admitted to Shenzhen Children’s Hospital in Shenzhen, China. Pneumonia was classified as severe or mild based on the Chinese guideline for the classification of pneumonia severity. Serum samples from all the children included in the study were tested for adenovirus DNA with a quantitative polymerase chain reaction. Clinical manifestations, laboratory examinations, and disease severity were compared between children with severe and mild pneumonia. Results A total of 111 immunocompetent children with adenovirus pneumonia (60 severe, 51 mild) were included. The median age was 40 months, and 64 patients were male. Five patients were admitted to the intensive care unit, and two underwent endotracheal intubation. All patients were discharged after recovery or improvement. Univariate analysis and binary logistic regression analysis showed that leukocytosis (OR = 1.1; 95% CI: 1.0 to 1.2; P = 0.033), co-infection with Mycoplasma pneumoniae (OR = 5.0; 95% CI: 2.1 to 12.3; P <  0.001), and high blood viral load (OR = 1.5; 95% CI: 1.2 to 2.0; P = 0.001) may be risk factors for severe adenovirus pneumonia. Conclusions Leukocytosis, co-infection with Mycoplasma pneumoniae, and high blood viral load may be risk factors for severe adenovirus pneumonia in immunocompetent children. Blood viral load may predict pneumonia severity.

scholarly journals Comparison of Three Cellular Assays to Predict the Course of CMV Infection in Liver Transplant Recipients

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 88
Author(s):  
Smaranda Gliga ◽  
Melanie Fiedler ◽  
Theresa Dornieden ◽  
Anne Achterfeld ◽  
Andreas Paul ◽  
...  
Keyword(s):  
Liver Transplant ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Cmv Infection ◽  
Cellular Assays ◽  
Risk Patients ◽  
Ifn Γ ◽  
Liver Transplant Recipients

To estimate protection from cytomegalovirus (CMV) replication after solid organ transplantation, CMV serology has been considered insufficient and thus CMV immunity is increasingly assessed by cellular in vitro methods. We compared two commercially available IFN-γ ELISpot assays (T-Track CMV and T-SPOT.CMV) and an IFN-γ ELISA (QuantiFERON-CMV). Currently, there is no study comparing these three assays. The assays were performed in 56 liver transplant recipients at the end of antiviral prophylaxis and one month thereafter. In CMV high- or intermediate-risk patients the two ELISpot assays showed significant correlation (p < 0.0001, r > 0.6) but the correlation of the ELISpot assays with QuantiFERON-CMV was weaker. Results of both ELISpot assays were similarly predictive of protection from CMV-DNAemia ≥500 copies/mL [CMV pp65 T-SPOT.CMV at the end of prophylaxis: area under curve (AUC) = 0.744, cut-off 142 spot forming units (SFU), sensitivity set to 100%, specificity 46%; CMV IE-1 T-Track CMV at month 1: AUC = 0.762, cut-off 3.5 SFU, sensitivity set to 100%, specificity 59%]. The QuantiFERON-CMV assay was inferior, reaching a specificity of 23% when setting the sensitivity to 100%. In conclusion, both CMV-specific ELISpot assays appear suitable to assess protection from CMV infection/reactivation in liver transplant recipients.

scholarly journals Cytomegalovirus in urinary sediment in patients with acute kidney injury

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sahra Pajenda ◽  
Sebastian Kapps ◽  
Daniela Gerges ◽  
Gregor Hoermann ◽  
Ludwig Wagner ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Allograft ◽  
Quantitative Polymerase Chain Reaction ◽  
Rna Extraction ◽  
Kidney Injury ◽  
Solid Organ ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Urine Sediment ◽  
Urinary Sediment

Abstract Background Immunosuppression in solid organ transplantation is associated with frequent infections. Renal allograft recipients are susceptible to opportunistic infections and can acquire human cytomegalovirus (HCMV) infections even within the allograft. There, HCMV can be found in both the glomerulus and tubular cells, but is mostly restricted to specific and circumscribed sites. Therefore, not all organ infections are identifiable by immunohistology for HCMV proteins in fine needle core biopsies. Thus, we performed a urinalysis study to search for HCMV-specific RNA transcripts in the urine sediment of patients with acute kidney injury. Methods Urinary sediment of 90 patients with acute kidney injury (AKI), including 48 renal transplant recipients (RTX) and 42 non-transplant recipients (nRTX), was collected from morning urine for RNA extraction and reverse transcription. The copy number of HCMV transcripts was evaluated using a UL132 HCMV-specific probe set and by real-time quantitative polymerase chain reaction (RT-qPCR). Results Of the 48 RTX patients, ten showed HCMV copies in their urine sediment cells. Within this group, three recipients had negative HCMV serology and received an allograft from an HCMV-seropositive donor. In addition, all three RTX patients on a belatacept-based immunosuppressive regimen had HCMV transcripts in their urine. Of the 42 nRTX patients, only two had detectable HCMV transcripts in urine sediment cells and both were under immunosuppression. Conclusions Ten immunosuppressed renal allograft recipients and two immunosuppressed non-transplant patients with AKI showed HCMV copies in urine sediment. Thus, HCMV positivity in urinary sediment appears to be associated with immunosuppression. This study describes a novel noninvasive method for detection of HCMV in urinary sediment. Whether all HCMV infections can be detected or only those with viral replication warrants further investigation.

A systematic review of post-transplant lymphoproliferative disorder after lung transplant.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19046-e19046
Author(s):  
Mobeen Zaka Haider ◽  
Zarlakhta Zamani ◽  
Fnu Kiran ◽  
Hasan Mehmood Mirza ◽  
Muhammad Taqi ◽  
...  
Keyword(s):  
Lymphoproliferative Disorder ◽  
Lung Transplant ◽  
Late Onset ◽  
Adult Population ◽  
Solid Organ Transplantation ◽  
Chemotherapeutic Agents ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Post Transplant ◽  
Lung Transplant Recipients

e19046 Background: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication after solid organ transplantation. This study aims to explore the association of PTLD diagnosed after lung transplant with infectious agents and immunosuppression regimen, explore types of PTLD, and their outcome. Methods: Following the PRISMA guideline, we searched the literature on PubMed, Cochrane, Embase, and clinicaltrials.gov. 1741 articles were screened and included five studies. Results: We analyzed data from five studies, n=13,643 transplant recipients with n=287 (2.10%) developed PTLD. Four studies showed that 32/63 (51%) PTLD patients were male and 31 (49%) were female. Three studies reported 53/55 (96.4%) patients were EBV positive at PTLD diagnosis. Courtwright. et al, reported that 217/224 (97%) PTLD was associated with either EBV positive donor or recipient. Four studies showed that the monomorphic B cell type 48/63 (76%) was the most common histological type of PTLD diagnosed with DLBCL the most common subtype 31/48 (64.6%). Data from 3 studies showed that the onset of PTLD following lung transplant varies with a median duration of 18.3 months (45 days to 20.2 years). Three studies showed that 26/55 (47.3%) patients had early-onset (≤ 1 yr of Tx) and 29/55 (52.7%) patients had late-onset PTLD (> 1 yr of Tx). Management of PTLD included a reduction in immunosuppression including corticosteroids, CNI, purine synthesis inhibitors, Rituximab, and chemotherapeutic agents. Three studies showed a mortality rate of 30/45 (66.7%) and 13/30 (43.3%) deaths were PTLD related. Conclusions: Our review concludes that PTLD is a serious complication, only 2% of lung transplant recipients developed PTLD. EBV seropositivity is the most factor associated with PTLD diagnosis. Monomorphic PTLD was reported as the most common type in the adult population and no association between gender and PTLD was found. The analysis shows that there is a slightly lower incidence of early (≤ 1 yr of Tx) than late-onset (> 1 yr of Tx) PTLD. Table 1 PTLD after a Lung transplant in adults - a review. [Table: see text]

scholarly journals Viral Enteritis in Solid-Organ Transplantation

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2019
Author(s):  
Anum Abbas ◽  
Andrea J. Zimmer ◽  
Diana Florescu
Keyword(s):  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Post Transplantation ◽  
Organ Transplant Recipients ◽  
Increased Risk ◽  
Viral Enteritis ◽  
Solid Organ Transplant Recipients

Solid organ transplant recipients are at increased risk for infections due to chronic immunosuppression. Diarrhea is a commonly encountered problem post transplantation, with infectious causes of diarrhea being a frequent complication. Viral infections/enteritides in solid organ transplant recipients often result from frequently encountered pathogens in this population such as cytomegalovirus, adenovirus, and norovirus. However, several emerging viral pathogens are increasingly being recognized as more sensitive diagnostic techniques become available. Treatment is often limited to supportive care and reduction in immunosuppression, though antiviral therapies mayplay a role in the treatment in certain diseases. Viral enteritis is an important entity that contributes to morbidity and mortality in transplant recipients.

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